COL19A1

Summary

COL19A1 (collagen type XIX alpha 1 chain, HGNC:2196) is a protein-coding gene on chromosome 6q13, encoding Collagen alpha-1(XIX) chain (Q14993). May act as a cross-bridge between fibrils and other extracellular matrix molecules.

This gene encodes the alpha chain of type XIX collagen, a member of the FACIT collagen family (fibril-associated collagens with interrupted helices). Although the function of this collagen is not known, other members of this collagen family are found in association with fibril-forming collagens such as type I and II, and serve to maintain the integrity of the extracellular matrix. The transcript produced from this gene has an unusually large 3’ UTR which has not been completely sequenced.

Source: NCBI Gene 1310 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 306 total — 1 pathogenic
• MANE Select transcript: NM_001858

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2196
Approved symbol	COL19A1
Name	collagen type XIX alpha 1 chain
Location	6q13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000082293
Ensembl biotype	protein_coding
OMIM	120165
Entrez	1310

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000455415, ENST00000476656, ENST00000478620, ENST00000483745, ENST00000620364

RefSeq mRNA: 1 — MANE Select: NM_001858 NM_001858

CCDS: CCDS4970

Canonical transcript exons

ENST00000620364 — 51 exons

Exon	Start	End
ENSE00001622916	70130182	70130223
ENSE00001634042	70121880	70121942
ENSE00003712350	70176520	70176564
ENSE00003713099	69938038	69938100
ENSE00003713186	69900239	69900338
ENSE00003713263	70142023	70142076
ENSE00003714297	69936785	69936910
ENSE00003714621	70034245	70034298
ENSE00003716880	70184703	70184738
ENSE00003717160	70142767	70142820
ENSE00003717414	70184871	70184915
ENSE00003718885	70144210	70144263
ENSE00003720201	70206901	70206978
ENSE00003721558	70102169	70102222
ENSE00003722151	69932783	69932863
ENSE00003723624	70163343	70163396
ENSE00003724090	70165941	70165985
ENSE00003724480	70171964	70172017
ENSE00003726391	70168171	70168215
ENSE00003726537	69929425	69929700
ENSE00003729270	70168025	70168075
ENSE00003730099	69962826	69962870
ENSE00003730558	70141893	70141928
ENSE00003730714	70180312	70180356
ENSE00003731425	70156127	70156231
ENSE00003733915	70137685	70137747
ENSE00003734306	70146659	70146703
ENSE00003735461	70144918	70145007
ENSE00003736128	69898948	69899022
ENSE00003736508	70156316	70156369
ENSE00003736791	70035904	70035939
ENSE00003737468	70199608	70199736
ENSE00003737659	70023627	70023680
ENSE00003738576	70180461	70180523
ENSE00003738950	69927909	69928032
ENSE00003739605	70149704	70149739
ENSE00003740795	69879536	69879658
ENSE00003741546	70161900	70161953
ENSE00003743276	70188075	70188245
ENSE00003744275	70146812	70146889
ENSE00003746253	70068423	70068476
ENSE00003746416	70156670	70156723
ENSE00003747009	70149992	70150045
ENSE00003747116	70190315	70190381
ENSE00003747244	70207147	70212468
ENSE00003749793	69866556	69866640
ENSE00003750127	70168655	70168681
ENSE00003750187	70151397	70151438
ENSE00003752064	70149851	70149904
ENSE00003752163	69959996	69960040
ENSE00003752671	70140954	70140989

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 77.48.

FANTOM5 (CAGE): breadth broad, TPM avg 3.4837 / max 592.8185, expressed in 387 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68459	2.3230	321
68460	0.7978	224
68461	0.1887	69
68457	0.0805	23
204049	0.0606	22
68458	0.0331	22

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.60	gold quality
mucosa of stomach	UBERON:0001199	75.65	gold quality
endothelial cell	CL:0000115	70.23	silver quality
epithelium of nasopharynx	UBERON:0001951	69.92	gold quality
cerebellar vermis	UBERON:0004720	69.91	silver quality
cortical plate	UBERON:0005343	69.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.17	gold quality
epithelial cell of pancreas	CL:0000083	68.73	gold quality
cerebellar cortex	UBERON:0002129	68.62	gold quality
cerebellum	UBERON:0002037	68.59	gold quality
cerebellar hemisphere	UBERON:0002245	68.50	gold quality
cartilage tissue	UBERON:0002418	67.93	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	65.98	gold quality
tibialis anterior	UBERON:0001385	65.80	silver quality
lymph node	UBERON:0000029	65.62	gold quality
popliteal artery	UBERON:0002250	65.04	gold quality
tibial artery	UBERON:0007610	65.02	gold quality
Brodmann (1909) area 23	UBERON:0013554	64.76	gold quality
middle temporal gyrus	UBERON:0002771	64.47	silver quality
urinary bladder	UBERON:0001255	64.35	gold quality
lower esophagus muscularis layer	UBERON:0035833	63.74	gold quality
lower esophagus	UBERON:0013473	63.72	gold quality
primary visual cortex	UBERON:0002436	63.60	gold quality
vermiform appendix	UBERON:0001154	62.59	gold quality
right atrium auricular region	UBERON:0006631	62.55	gold quality
tonsil	UBERON:0002372	62.52	gold quality
prefrontal cortex	UBERON:0000451	62.32	gold quality
granulocyte	CL:0000094	62.16	gold quality
cardiac atrium	UBERON:0002081	62.03	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.36
E-GEOD-111727	no	125.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

340 targeting COL19A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-3662	99.99	73.82	5684

Literature-anchored findings (GeneRIF, showing 4)

• collagen IX has unique cell adhesion properties when compared with other collagens, and it provides a novel mechanism for cell adhesion to cartilaginous matrix (PMID:15383545)
• The NC2 domain of collagen XIX and probably of other FACITs is responsible for chain selection and trimerization (PMID:18845531)
• Type XIX collagen is a new partner in the interactions between tumor cells and their microenvironment. (Review) (PMID:27491275)
• Naturally occurring interruptions in nonfibrillar collagen play key roles in molecular flexibility, collagen degradation, and ligand binding. This study focused on a G5G type natural interruption sequence G-POALO-G from human type XIX collagen, a homotrimer collagen, as this sequence possesses distinct properties compared with those of a pathological similar Gly mutation sequence in collagen mimic peptides. (PMID:29376320)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Col19a1	ENSMUSG00000026141
rattus_norvegicus	Col19a1	ENSRNOG00000012759

Paralogs (23): C1QTNF3 (ENSG00000082196), PDCD7 (ENSG00000090470), COL10A1 (ENSG00000123500), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), COL8A1 (ENSG00000144810), C1QTNF2 (ENSG00000145861), C1QC (ENSG00000159189), C1QTNF7 (ENSG00000163145), C1QL3 (ENSG00000165985), COL8A2 (ENSG00000171812), C1QTNF4 (ENSG00000172247), C1QB (ENSG00000173369), C1QA (ENSG00000173372), C1QTNF1 (ENSG00000173918), ADIPOQ (ENSG00000181092), OTOL1 (ENSG00000182447), C1QTNF8 (ENSG00000184471), C1QL4 (ENSG00000186897), C1QTNF9B (ENSG00000205863), C1QTNF5 (ENSG00000223953), C1QTNF9 (ENSG00000240654)

Protein

Protein identifiers

Collagen alpha-1(XIX) chain — Q14993 (reviewed: Q14993)

Alternative names: Collagen alpha-1(Y) chain

All UniProt accessions (3): Q14993, A0A087WVJ7, Q5JVU1

UniProt curated annotations — full annotation on UniProt →

Function. May act as a cross-bridge between fibrils and other extracellular matrix molecules. Involved in skeletal myogenesis in the developing esophagus. May play a role in organization of the pericellular matrix or the sphinteric smooth muscle.

Subunit / interactions. Oligomer; disulfide-linked.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Localized to vascular, neuronal, mesenchymal, and some epithelial basement membrane zones in umbilical cord.

Post-translational modifications. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.

Domain organisation. The numerous interruptions in the triple helix may make this molecule either elastic or flexible.

Similarity. Belongs to the fibril-associated collagens with interrupted helices (FACIT) family.

RefSeq proteins (1): NP_001849* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008160	Collagen	Repeat
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR048287	TSPN-like_N	Domain
IPR050149	Collagen_superfamily	Family

Pfam: PF01391

UniProt features (52 total): compositionally biased region 13, domain 12, sequence conflict 10, region of interest 9, sequence variant 5, signal peptide 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14993-F1	55.83	0.15

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-8948216	Collagen chain trimerization

MSigDB gene sets: 273 (showing top): MORF_ITGA2, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_MUSCLE_TISSUE_DEVELOPMENT, MORF_MSH3, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, TGCACTT_MIR519C_MIR519B_MIR519A, GOCC_COLLAGEN_TRIMER, GCANCTGNY_MYOD_Q6, ATACCTC_MIR202, MORF_BRCA1, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MORF_RAD51L3, GOBP_CELL_CELL_ADHESION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT

GO Biological Process (7): skeletal system development (GO:0001501), cell adhesion (GO:0007155), skeletal muscle tissue development (GO:0007519), cell differentiation (GO:0030154), extracellular matrix organization (GO:0030198), cell-cell adhesion (GO:0098609), muscle organ development (GO:0007517)

GO Molecular Function (3): extracellular matrix structural constituent (GO:0005201), extracellular matrix structural constituent conferring tensile strength (GO:0030020), protein-macromolecule adaptor activity (GO:0030674)

GO Cellular Component (4): extracellular region (GO:0005576), collagen trimer (GO:0005581), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Degradation of the extracellular matrix	1
Collagen formation	1
Collagen biosynthesis and modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
cellular process	1
striated muscle tissue development	1
skeletal muscle organ development	1
cellular developmental process	1
extracellular structure organization	1
external encapsulating structure organization	1
cell adhesion	1
animal organ development	1
muscle structure development	1
structural molecule activity	1
extracellular matrix	1
extracellular matrix structural constituent	1
protein binding	1
molecular adaptor activity	1
cellular anatomical structure	1
protein-containing complex	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1

Protein interactions and networks

STRING

978 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL19A1	VWA1	Q6PCB0	840
COL19A1	CNIH3	Q8TBE1	539
COL19A1	CNIH1	O95406	532
COL19A1	COL18A1	P39060	473
COL19A1	ZNF573	Q86YE8	469
COL19A1	COL15A1	P39059	457
COL19A1	SEC16B	Q96JE7	445
COL19A1	ABCA13	Q86UQ4	445
COL19A1	APOB	P04114	439
COL19A1	HSPG2	P98160	427
COL19A1	MCTP2	Q6DN12	418
COL19A1	PRDM15	P57071	417
COL19A1	UNC80	Q8N2C7	417
COL19A1	CMC2	Q9NRP2	410
COL19A1	MAST4	O15021	410
COL19A1	TP53I11	O14683	410

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350

BioGRID (4): COL19A1 (Co-fractionation), COL19A1 (Co-fractionation), COL19A1 (Co-fractionation), COL19A1 (Affinity Capture-MS)

ESM2 similar proteins: A0A060WQA3, A0MSJ1, A5PN28, A6NHN0, A8WR59, C0HLN2, C7DZK3, O35167, O35348, O76368, O88207, P08122, P08572, P12106, P12107, P12108, P13942, P20849, P20850, P20908, P20909, P25067, P25940, P53420, P83371, P98085, Q01955, Q03637, Q05722, Q07092, Q07643, Q0VF58, Q14031, Q14055, Q14993, Q17RW2, Q28083, Q30D77, Q32S24, Q4ZJM7

Diamond homologs: P12106, P13944, P20849, P20850, Q05722, Q07092, Q0VF58, Q14993, Q60847, Q641F3, Q8BLX7, Q8NFW1, Q96P44, Q99715, Q9JI03, A0A1D5NSM8, A2AX52, A6H584, A6NMZ7, A6QLN9, A8TX70, E1BMV3, O00339, O08746, O15232, O35701, O42163, O42401, O43405, O89029, O95460, P05099, P12111, P15989, P18614, P20785, P21941, P32018, P34576, P51942

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

306 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	182
Likely benign	15
Benign	92

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1456629	NC_000006.11:g.(?70386050)(71012627_?)del	Pathogenic

SpliceAI

7835 predictions. Top by Δscore:

Variant	Effect	Δscore
6:69898942:A:AG	acceptor_gain	1.0000
6:69898943:A:G	acceptor_gain	1.0000
6:69898947:GAA:G	acceptor_gain	1.0000
6:69898947:GAAGA:G	acceptor_gain	1.0000
6:69900159:A:G	donor_gain	1.0000
6:69900237:A:AG	acceptor_gain	1.0000
6:69900237:A:C	acceptor_loss	1.0000
6:69900237:AG:A	acceptor_gain	1.0000
6:69900238:G:GG	acceptor_gain	1.0000
6:69900238:GG:G	acceptor_gain	1.0000
6:69900238:GGT:G	acceptor_gain	1.0000
6:69900334:ACTAT:A	donor_gain	1.0000
6:69900335:CTAT:C	donor_gain	1.0000
6:69900336:TAT:T	donor_gain	1.0000
6:69900336:TATG:T	donor_loss	1.0000
6:69900337:AT:A	donor_gain	1.0000
6:69900337:ATG:A	donor_loss	1.0000
6:69900338:TG:T	donor_loss	1.0000
6:69900339:G:GG	donor_gain	1.0000
6:69900339:GTAA:G	donor_loss	1.0000
6:69900340:T:TC	donor_loss	1.0000
6:69900341:AA:A	donor_loss	1.0000
6:69927907:A:AG	acceptor_gain	1.0000
6:69927908:G:GT	acceptor_gain	1.0000
6:69927908:GT:G	acceptor_gain	1.0000
6:69927908:GTA:G	acceptor_gain	1.0000
6:69927908:GTAA:G	acceptor_gain	1.0000
6:69929697:GGAT:G	donor_gain	1.0000
6:69929698:GAT:G	donor_gain	1.0000
6:69929698:GATG:G	donor_gain	1.0000

AlphaMissense

7247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:69927991:T:A	W117R	0.991
6:69927991:T:C	W117R	0.991
6:69928000:T:A	W120R	0.990
6:69928000:T:C	W120R	0.990
6:70184907:G:A	G950R	0.988
6:70184907:G:C	G950R	0.988
6:69932790:T:C	L225P	0.986
6:70188076:G:A	G953D	0.986
6:70184899:G:A	G947D	0.985
6:69927962:G:C	R107P	0.983
6:69929547:G:C	W171C	0.983
6:69929547:G:T	W171C	0.983
6:70184908:G:A	G950E	0.983
6:70184898:G:C	G947R	0.982
6:70188084:G:A	G956R	0.982
6:70188084:G:C	G956R	0.982
6:70207212:T:A	C1123S	0.981
6:70207213:G:C	C1123S	0.981
6:70171982:G:A	G863R	0.980
6:70171982:G:C	G863R	0.980
6:70172000:G:A	G869R	0.980
6:70172000:G:C	G869R	0.980
6:70199736:G:C	G1075R	0.980
6:70150029:G:A	G674D	0.979
6:70206910:G:A	G1078E	0.979
6:70206918:G:A	G1081R	0.978
6:70206918:G:C	G1081R	0.978
6:70188084:G:T	G956W	0.977
6:70199691:G:T	G1060W	0.976
6:70156679:G:A	G750R	0.975

dbSNP variants (sampled 300 via entrez): RS1000002560 (6:70123322 G>T), RS1000006792 (6:70023494 T>C), RS1000014791 (6:69926570 G>C), RS1000018552 (6:70064092 A>G), RS1000022834 (6:69989024 T>C), RS1000031392 (6:70183197 G>T), RS1000043910 (6:70036737 T>A,C), RS1000062486 (6:70019847 A>C), RS1000074521 (6:69923299 A>G), RS1000109004 (6:70129605 C>G,T), RS1000112674 (6:70170897 G>A), RS1000120562 (6:69879968 A>G), RS1000124824 (6:69923523 T>C), RS1000153949 (6:70166169 A>G), RS1000177635 (6:70178435 A>G,T)

Disease associations

OMIM: gene MIM:120165 | disease phenotypes: MIM:277380

GenCC curated gene-disease

Mondo (1): methylmalonic aciduria and homocystinuria type cblF (MONDO:0010183)

Orphanet (1): Methylmalonic acidemia with homocystinuria type cblF (Orphanet:79284)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000635_7	Response to statin therapy	4.000000e-06
GCST006665_4	Social science traits (pleiotropy) (HIPO component 1)	2.000000e-09
GCST008157_16	Body fat mass	7.000000e-06
GCST008158_150	Body mass index	7.000000e-06
GCST010676_6	Leukoderma in response to rhododendrol	2.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0007006	depressive symptom measurement
EFO:0007660	neuroticism measurement
EFO:0007869	wellbeing measurement
EFO:0004340	body mass index

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564747	Methylmalonic Aciduria and Homocystinuria, CblF Type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
FR900359	decreases phosphorylation	1
Sunitinib	increases expression	1
Phthalic Acids	affects methylation	1
Valproic Acid	decreases methylation	1
Asbestos, Serpentine	increases methylation	1
Coal Ash	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.